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Low dose Naltrexone for induction of remission in inflammatory bowel disease patients

机译:低剂量纳曲酮诱导炎症性肠病患者缓解

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Around 30% of patients with inflammatory bowel disease (IBD) are refractory to current IBD drugs or relapse over time. Novel treatments are called for, and low dose Naltrexone (LDN) may provide a safe, easily accessible alternative treatment option for these patients. We investigated the potential of LDN to induce clinical response in therapy refractory IBD patients, and investigated its direct effects on epithelial barrier function. Patients not in remission and not responding to conventional therapy were offered to initiate LDN as a concomitant treatment. In total 47 IBD patients prescribed LDN were followed prospectively for 12?weeks. Where available, endoscopic remission data, serum and biopsies were collected. Further the effect of Naltrexone on wound healing (scratch assay), cytokine production and endoplasmic reticulum (ER) stress (GRP78 and CHOP western blot analysis, immunohistochemistry) were investigated in HCT116 and CACO2 intestinal epithelial cells, human IBD intestinal organoids and patient samples. Low dose Naltrexone induced clinical improvement in 74.5%, and remission in 25.5% of patients. Naltrexone improved wound healing and reduced ER stress induced by Tunicamycin, lipopolysaccharide or bacteria in epithelial barriers. Inflamed mucosa from IBD patients showed high ER stress levels, which was reduced in patients treated with LDN. Cytokine levels in neither epithelial cells nor serum from IBD patients were affected. Naltrexone directly improves epithelial barrier function by improving wound healing and reducing mucosal ER stress levels. Low dose Naltrexone treatment is effective and safe, and could be considered for the treatment of therapy refractory IBD patients.
机译:大约30%的炎症性肠病(IBD)患者对目前的IBD药物难治或随时间复发。需要新的治疗方法,低剂量纳曲酮(LDN)可能为这些患者提供安全,容易获得的替代治疗选择。我们研究了LDN在难治性IBD患者中诱导临床反应的潜力,并研究了其对上皮屏障功能的直接影响。未缓解且对常规疗法无反应的患者可以接受LDN作为伴随治疗。总共对47名接受LDN处方的IBD患者进行了为期12周的随访。在可获得的情况下,收集内窥镜检查缓解数据,血清和活检样本。进一步在HCT116和CACO2肠上皮细胞,人IBD肠类器官和患者样品中研究了纳曲酮对伤口愈合(划痕测定),细胞因子产生和内质网(ER)应激(GRP78和CHOP Western blot分析,免疫组化)的影响。低剂量纳曲酮引起的临床改善率为74.5%,缓解的患者为25.5%。纳曲酮改善上皮屏障中的衣霉素,脂多糖或细菌诱导的伤口愈合并减少内质网应激。 IBD患者发炎的黏膜表现出较高的内质网应激水平,而接受LDN治疗的患者则减轻了。 IBD患者的上皮细胞和血清中的细胞因子水平均未受影响。纳曲酮通过改善伤口愈合和降低粘膜内质网应激水平直接改善上皮屏障功能。低剂量纳曲酮治疗是安全有效的,可以考虑用于难治性IBD患者的治疗。

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